TY - JOUR
T1 - Crystal Structures of a Ligand-free MthK Gating Ring
T2 - Insights into the Ligand Gating Mechanism of K+ Channels
AU - Ye, Sheng
AU - Li, Yang
AU - Chen, Liping
AU - Jiang, Youxing
N1 - Funding Information:
We thank A. Alam and P. Thibodeau for manuscript preparation; Drs. J. Cabral, R. MacKinnon, and E. Goldsmith for discussion and critical review of the manuscript. Use of the Argonne National Laboratory Structural Biology Center beamlines at the Advanced Photon Source was supported by the US Department of Energy, Office of Energy Research. We thank the beamline staff for assistance in data collection. This work was supported by grants from the National Institutes of Health (GM071621), the Searle Scholars Program (04-A-101), and the Robert A. Welch Foundation (I-1578) to Y.J.
PY - 2006/9/22
Y1 - 2006/9/22
N2 - MthK is a prokaryotic Ca2+-gated K+ channel that, like other ligand-gated channels, converts the chemical energy of ligand binding to the mechanical force of channel opening. The channel's eight ligand-binding domains, the RCK domains, form an octameric gating ring in which Ca2+ binding induces conformational changes that open the channel. Here we present the crystal structures of the MthK gating ring in closed and partially open states at 2.8 Å, both obtained from the same crystal grown in the absence of Ca2+. Furthermore, our biochemical and electrophysiological analyses demonstrate that MthK is regulated by both Ca2+ and pH. Ca2+ regulates the channel by changing the equilibrium of the gating ring between closed and open states, while pH regulates channel gating by affecting gating-ring stability. Our findings, along with the previously determined open MthK structure, allow us to elucidate the ligand gating mechanism of RCK-regulated K+ channels.
AB - MthK is a prokaryotic Ca2+-gated K+ channel that, like other ligand-gated channels, converts the chemical energy of ligand binding to the mechanical force of channel opening. The channel's eight ligand-binding domains, the RCK domains, form an octameric gating ring in which Ca2+ binding induces conformational changes that open the channel. Here we present the crystal structures of the MthK gating ring in closed and partially open states at 2.8 Å, both obtained from the same crystal grown in the absence of Ca2+. Furthermore, our biochemical and electrophysiological analyses demonstrate that MthK is regulated by both Ca2+ and pH. Ca2+ regulates the channel by changing the equilibrium of the gating ring between closed and open states, while pH regulates channel gating by affecting gating-ring stability. Our findings, along with the previously determined open MthK structure, allow us to elucidate the ligand gating mechanism of RCK-regulated K+ channels.
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U2 - 10.1016/j.cell.2006.08.029
DO - 10.1016/j.cell.2006.08.029
M3 - Article
C2 - 16990139
AN - SCOPUS:33748622291
SN - 0092-8674
VL - 126
SP - 1161
EP - 1173
JO - Cell
JF - Cell
IS - 6
ER -